Glycated Apolipoprotein A-IV Induces Atherogenesis in Patients With CAD in Type 2 Diabetes.
J Am Coll Cardiol
; 70(16): 2006-2019, 2017 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-29025558
ABSTRACT
BACKGROUND:
Nonenzymatic glycation of apolipoproteins plays a role in the pathogenesis of the vascular complications of diabetes.OBJECTIVES:
This study investigated whether apolipoprotein (apo) A-IV was glycated in patients with type 2 diabetes mellitus (T2DM) and whether apoA-IV glycation was related to coronary artery disease (CAD). The study also determined the biological effects of glycated apoA-IV.METHODS:
The authors consecutively enrolled 204 patients with T2DM without CAD (Group I), 515 patients with T2DM with CAD (Group II), and 176 healthy subjects (control group) in this study. ApoA-IV was precipitated from ultracentrifugally isolated high-density lipoprotein, and its glycation level was determined based on Western blotting densitometry (relative intensity of apoA-IV glycation). ApoA-IV NÆ-(carboxylmethyl) lysine (CML) modification sites were identified by mass spectrometry in 37 control subjects, 63 patients in Group I, and 138 patients in Group II. Saline or glycated apoA-IV (g-apoA-IV) generated by glyoxal culture was injected into apoE-/- mice to evaluate atherogenesis, and was also used for the cell experiments.RESULTS:
The relative intensity and the abundance of apoA-IV glycation were associated with the presence and severity of CAD in patients with T2DM (all p < 0.05). The experiments showed that g-apoA-IV induced proinflammatory reactions in vitro and promoted atherogenesis in apoE-/- mice through the nuclear receptor NR4A3. G-apoA-IV with mutations (K-A) at high-frequency glycation sites exhibited more weakened proinflammatory and atherogenic effects than did g-apoA-IV both in vitro and in vivo.CONCLUSIONS:
ApoA-IV glycation is associated with CAD severity in patients with T2DM, and g-apoA-IV induces atherogenesis through NR4A3 in apoE-/- mice.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas A
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Doença da Artéria Coronariana
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Diabetes Mellitus Tipo 2
/
Aterosclerose
Limite:
Aged
/
Animals
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article